POS1207 SEROCONVERSION AFTER A THIRD COVID-19 VACCINATION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH (ULTRA-)LOW DOSE RITUXIMAB WITH A PREVIOUS INSUFFICIENT HUMORAL RESPONSE IS DEPENDENT ON RITUXIMAB DOSAGE
Authors: C. Van der Togt, D. Ten Cate, B. Van den Bemt, J. Rahamat-Langendoen, N. Den Broeder, A. Den Broeder
Journal: Annals of the Rheumatic Diseases (2022)

Background Around 60% of rheumatoid arthritis (RA) patients treated with ≥1000 mg rituximab (RTX) has an insufficient deemed humoral response after two COVID-19 vaccinations.[1] Recent research shows that a third COVID-19 vaccine may actually lead to a humoral response in 27% of patients with a previous non-response.[2] After two-dose vaccination, both ultra-low dose (ULD) 200 mg RTX and a longer time between latest RTX and vaccination were positively associated with sufficient response.[3] Yet, no data is available on the effect of those variables after a third vaccination in these ULD patients with an insufficient response after two vaccinations. Objectives To investigate the role of dosage and relative timing of RTX and vaccination on humoral response after a third COVID-19 vaccine in RA patients treated with RTX with insufficient humoral response after two COVID-19 vaccinations. Methods We included RA patients treated with ≥1 RTX dose in the year previous to the first vaccine from the COVAC cohort (Netherlands Trial Register, NL9342), who had an insufficient humoral response after two COVID-19 vaccines. Humoral response was measured 2-6 weeks after the third vaccine. As there is still a lot of uncertainty about a serological correlate of protection, we dichotomized between ‘sufficient’ and ‘insufficient’ response based on the cut-off of the specific assay used. Univariable logistic regression was used to investigate the association between dosing and timing, and sufficient response. Results Eighty-nine patients had an antibody measurement performed within the right time-frame and could be included (Table 1). Overall, 17 patients (19%) had a sufficient antibody response. Proportion of patients with sufficient humoral response was higher when the latest dose was 200 mg compared to 500 and 1000 mg (38% versus 21% versus 13% (Figure 1); odds ratio 200 versus 1000 mg (OR) 4.25; 95% confidence interval (CI) 0.99 to 18.29 (p=0.052), and especially when the dose was already 200 mg before the first vaccination (OR 4.63; 95% CI 1.08-19.84 (p=0.039)). Time since latest RTX infusion was not significantly associated with sufficient response after third vaccination (OR 1.00; 95% CI 1.00-1.01 (p=0.15)). Table 1. Characteristics and outcomes sorted by rituximab dose before first vaccination 200 mg (n=13) 500 mg (n=34) 1000 mg (n=42) Age (years) ‡ 66 ± 11 67 ± 11 65 ± 13 Female sex 7 (54%) 29 (85%) 29 (69%) Disease duration (years) † 21 (16-26) 18 (8-26) 14 (5-23) RF and/or ACPA positive 13 (100%) 27 (80%) 31 (74%) Concomitant csDMARD use at baseline 7 (54%) 21 (62%) 29 (69%) Duration of RTX use (years) ‡ 5.8 ± 3.1 4.9 ± 3.1 4.5 ± 3.2 Days between latest RTX and 3 rd vaccine † 127 (100-160) 117 (99-153) 126 (91-150) Latest RTX dose before 3 rd vaccine 200 mg 12 (92%) 1 (3%) 0 (0%) 500 mg 1 (8%) 31 (91%) 5 (12%) 1000 mg 0 (0%) 2 (6%) 37 (88%) Sufficient humoral response after 3 rd vaccine 5 (38%) 7 (21%) 5 (12%) Either displayed as number (percentage), median (interquartile range) † or mean ± standard deviation ‡ . Figure 1. Humoral response rate after third COVID-19 vaccination sorted by baseline rituximab dose Conclusion Our study shows that a third COVID-19 vaccine can induce sufficient humoral response in a relevant proportion of (ultra-)low dose RTX treated RA patients who did not respond to the first two vaccinations, and that lower RTX dosing is associated with significant higher proportion of patients with sufficient humoral response. In contrast to the analysis after two vaccine doses, time since latest infusion was not significantly associated with response. References [1]Furer V, et al. Ann Rheum Dis. 2021 Oct;80(10):1330-1338. [2]Bonelli M, et al. Ann Rheum Dis. 2022 Jan 13:annrheumdis-2021-221558. [3]Van der Togt, CJT et al., Humoral Response to Coronavirus Disease-19 Vaccines is Dependent on Dosage and Timing Since Latest Infusion in Patients with Rheumatoid Arthritis Treated with Rituximab, submitted . Acknowledgements We thank the staff of the rheumatology outpatient clinic of the Sint Maartenskliniek for performing blood sampling for this study, and Paul Daemen for performing the assays. Disclosure of Interests Celeste van der Togt: None declared, david ten cate: None declared, Bart van den Bemt Speakers bureau: UCB, Pfizer, Sanofi-Aventis, Galapagos, Amgen en Eli Lilly, Janette Rahamat-Langendoen: None declared, Nathan den Broeder: None declared, Alfons den Broeder Grant/research support from: Abbvie, Galapagos, Pfizer, Novartis, Lilly, Sanofi, Gilead